Tau Islands, Actin Locks, and Automated Kymograph Analysis
Cohesive Tau Islands Shield and Protect the Microtubule Lattice
Tau, a microtubule-associated protein in the brain, is primarily recognized for its role in neurodegenerative diseases. In fact, the term “tauopathy” was specifically coined to reference neuronal disorders pathologically defined by tau protein aggregates. But what is the physiological function of tau in healthy neurons? This question has largely alluded researchers to date and is made more intriguing in that tau is an intrinsically disordered protein with microtubule-regulating capabilities.
The Ori-McKenney/McKenney and Lánský/Braun research groups explore the mechanism and function of tau-mediated microtubule regulation in a pair of papers published in Nature Cell Biology. Using in vitro reconstitution approaches, the authors find that tau self-organizes into cohesive “islands” that shield and protect the microtubule lattice. Tau islands prevent severing enzymes (i.e. katanin and spastin) from accessing microtubule surfaces and function as roadblocks against molecular motors (i.e. kinesin-1). More processive motors (i.e. kinesin-8 and dynein), however, can penetrate the islands, revealing that self-associated tau molecules form a selectively permissible barrier. Collectively, these studies provide a framework for understanding tau functions in physiological and disease-states.
“We anticipate that other intrinsically disordered axonal proteins display a similar cooperative behavior and potentially compete with tau in regulating access to the microtubule surface.”
–Siahaan et al.
Tools and Methods
KymoButler, A Deep Learning Software For Automated Kymograph Analysis
Jakobs, Dimitracopoulos, and Franze | eLife
A new software package harnesses Machine Learning for the automated analysis of dynamic biological processes.
Reviews and Perspectives
The Cytoskeleton as a Modulator of Aging and Neurodegeneration
Kounakis and Tavernarakis | Advances in Experimental Medicine and Biology
Decades of research link actin, microtubules, and intermediate filaments with organismal aging and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s.
Juraj Simunić and Radhika Subramanian recap highlights from the first “Mitotic Spindle: From Living and Synthetic Systems to Theory” research conference held in Split, Croatia last spring.
–Journal of Cell Science
• spindle architecture
• in vitro reconstitution
• kinetochore structure
• spindle assembly
• microtubule regulation
Journal Club Picks
- Epithelial cells actively migrate within intestinal crypts using actin-rich basal protrusions.
Krndija et al. | Hannezo and Vignjevic Labs | Science
- An actin-based periodic skeleton mediates signal transduction in neurons.
Zhou et al. | Zhuang Lab | Science
- EB1 targets specific microtubule end structures regardless of hydrolysis state.
Reid et al. | Gardner Lab | eLife
- A distinct tubulin off-rate underlies the dynamic behavior of microtubule minus ends.
Strothman et al. | Zanic Lab | Journal of Cell Biology
- Branched microtubule nucleation is observed for the first time in live cells.
Verma and Maresca | Maresca Lab | Journal of Cell Biology
- The meiotic spindle maintains its shape for several days via dynamic remodeling.
Costa and Ohkura | Ohkura Lab | Journal of Cell Biology
- The distribution of astral versus spindle microtubules shifts during brain development.
Vargas-Hurtado et al. | Marthiens and Basto Labs | Current Biology
- Interphase microtubules facilitate DNA repair via linkages through the nuclear envelope.
Zhurinsky et al. | Chang and Daga Labs | Molecular Biology of the Cell
- An actin-mediated molecular lock maintains body-axis elongation in developing embryos.
Lardennois et al. | Labouesse Lab | Nature
- Actin-microtubule crosslinks determine the viscoelasticity of cytoskeleton composites.
Ricketts et al. | Robertson-Anderson Lab | Scientific Reports
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